eMultipleSclerosis Review, Volume 1, Issue 6

HOME

NEWSLETTER
ARCHIVE

CME
INFORMATION

PROGRAM
DIRECTORS

EDIT
PROFILE

RECOMMEND TO
A COLLEAGUE

VOLUME 1 - ISSUE 6

Editor's Note: Important new findings in MS research were presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Among them were studies comparing the efficacies of two disease modifying therapy (DMT) agents, fingolimod and natalizumab; an investigation into the outcome of halting DMT therapy in stable patients; and the factors influencing patient-perceived risks and disease acceptance.

There are few controlled clinical studies comparing the relative efficacies of the newer MS disease modifying therapies. One new head-to-head comparison1 of fingolimod and natalizumab seems to indicate an advantage of natalizumab over fingolimod in decreasing MS disease activity, while another shows no difference.

In the first study, prospective data analysis revealed a significantly lower proportion of patients with at least one relapse within the first year of treatment in natalizumab-treated patients (n =326; 21.1%) compared to fingolimod-treated patients (n=303; 30.4%) (p=0.0092). Similarly, fewer gadolinium enhancing lesions were noted with natalizumab versus fingolimod-treated patients (9.3% vs. 29.8%; p< 0.0001), while new T2-lesions were seen with in only 10.6% of natalizumab-treated patients as compared to 29.6% in patients taking fingolimod (p<0.0001).

Evidence from a different comparative study², however, showed no difference or trend in disease activity between the same two drugs. This study utilized propensity score matching (PSM), a technique that reduces bias from imbalances in baseline co-variates.

Patients were matched by PSM, with unmatchable subjects excluded (n= 1201 total/ 884 matched). The study revealed an on-treatment relapse rate of 0.31 in natalizumab-treated patients versus 0.30 with fingolimod (n.s.). The Kaplan-Meyer mean time from treatment start to first relapse was 2.06 years for natalizumab and 2.10 years for fingolimod (n.s.). The Cox regression hazard ratio for a first relapse was 1.04 after PSM and further inclusion of the matching covariates. Additional studies will be needed to clarify the comparative efficacy of these two drugs.

Stable MS patients who discontinue their DMT showed a decreased tendency for relapse and an increased tendency for sustained disability progression, compared to patients who continued their therapy, according to outcomes of a new prospective study.³

In the study, DMT 'stayers' (n=140) were matched 1:1 by PSM with DMT 'stoppers' (n = 140) revealing a total of 77 first relapse events and 38 sustained disability progression events across the four year follow-up period. DMT stoppers had a non-significantly decreased risk of relapse compared to stayers and a non-significantly increased risk of sustained disability. Overall, these results must be interpreted in light of the types of patients who stop DMTs (i.e. fewer relapses than those who continue DMT treatment).

Finally, MS patients' grasp of their disease can impact disease acceptance and adherence to therapy. According to one study presented,⁴ factors such as assumed or perceived treatment efficacy influence risk perception and disease acceptance. Patients are accepting of treatments with the potential to improve MS, in spite of associated life-threatening risks. Furthermore, unrealistic expectations of benefits and risk might be a major reason for poor adherence. Conversely, adherence rates are often higher in patients with a more aggressive disease course, indicating that MS threat is a major modulator of risk acceptance.

1. D. Laplaud, L.Barbin, C. Rousseau, et. al. Comparative Efficacy of fingolimod versus natalizumab in MS: a prospective multicenter observational study. ECTRIMS Online Library. Laplaud D. Oct 9, 2015; 116627
2. N. Koch-Henriksen, M. Magyari, P.S. Sorensen. A comparison of MS disease activity between patients treated with natalizumab and fingolimod. ECTRIMS Online Library. Koch-Henriksen N. Oct 9, 2015; 116637
3. I. Kister, T. Spelman, R Alroughani, et. al. Are stable MS patients who stop their disease modifying therapy (DMT) at increased risk for relapses and disability progression compared to patients who continue on DMT's? A propensity-score matched analysis of the MSBase registrants. ECTRIMS Online Library. Kister I. Oct 8, 2015; 116635
4. C. Heesen. Patient perceived risk and acceptance. ECTRIMS Online Library. Heesen C. Oct 8, 2015; 116738.

Incorporating MRI Results in Treatment Decision Making

Our guest author is Benjamin M. Greenberg, MD, MHS, Associate Professor, Department of Neurology & Neurotherapeutics, Pediatrics at UT Southwestern Medical Center in Dallas.

After participating in this activity, the participant will demonstrate the ability to:

Discuss the prognostic significance of MRI findings at the time of diagnosis.
Identify the prognostic significance of MRI changes during the course of disease modifying therapy.
Describe how the evolving landscape of disease modifying therapies affects risk/benefit calculations when considering therapy changes.

This discussion, offered as a downloadable audio file and companion transcript, covers the important topic of incorporating MRI results into this current era of expanding therapy options for patients with MS in the format of case-study scenarios for the clinical practice. This program is a follow up to the Volume 1, Issue 5 eMultipleSclerosis Review newsletter-Incorporating MRI Results in Treatment Decision Making.

Unlabeled/Unapproved Uses
Dr. Greenberg has disclosed that he has received grant support from Acorda Therapeutics, Biogen, Chugai Pharmaceutical Co., and MedImmune. He has served as a consultant for MedImmune, Novartis, and EMD Serono.


	MEET THE AUTHOR


			Benjamin M. Greenberg, MD, MHS Associate Professor, Department of Neurology & Neurotherapeutics, Pediatrics UT Southwestern Medical Center Dallas, Texas

Guest Faculty Disclosure
Dr. Greenberg has indicated that there will be no references to unlabeled/unapproved uses of drugs or products.

Release Date:	Expiration Date:
November 19, 2015	November 18, 2017


	OTHER RESOURCES

	Download the podcast transcript Go to the companion newsletter

PROGRAM DIRECTORS

Arun Venkatesan, MD, PhD
Associate Professor of Neurology
Director, Johns Hopkins Encephalitis Center
Associate Program Director, Neurology Residency
Johns Hopkins University School of Medicine
Baltimore, Maryland

Scott Douglas Newsome, DO
Assistant Professor of Neurology
Director, Neurology Outpatient Services
Director, Neurology Infusion Center
Johns Hopkins University School of Medicine
Baltimore, Maryland



	CME/CE INFORMATION


	ACCREDITATION STATEMENT The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. CREDIT DESIGNATIONS Podcast: The Johns Hopkins University School of Medicine designates this enduring material for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity

	DISCLAIMER STATEMENT STATEMENT OF RESPONSIBILITY STATEMENT OF NEED	INTENDED AUDIENCE CONFIDENTIALITY DISCLAIMER FOR CME ACTIVITY PARTICIPANTS HARDWARE & SOFTWARE REQUIREMENTS COMPLETE CME INFORMATION
All rights reserved - The Johns Hopkins University School of Medicine. Copyright 2015. This activity was developed in collaboration with DKBmed.